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This was a 1-year, multicenter, open-label, long-term study to assess the safety of REL-1017 once daily (QD) as monotherapy or as adjunctive treatment of Major Depressive Disorder. Adjunctive study participants continued to take their current antidepressant therapy in addition to the study drug for the duration of the treatment period.
This was a multicenter, open-label, long-term study of REL-1017 to evaluate the long-term safety and long-term durability of response in patients with MDD. Patients who completed previous randomized, double-blind Phase 3 trials (NCT04688164, NCT04855747, NCT05081167) of REL-1017 as adjunctive therapy or monotherapy for MDD were asked to continue treatment with REL-1017 25 mg daily for up to 1 year. De novo patients who satisfied inclusion/exclusion criteria also were enrolled and received a 75 mg loading dose of REL-1017 on Day 1 followed by a maintenance dose of 25 mg REL-1017 daily for the remainder of the study (Days 2-365). When REL-1017 was administered as adjunctive treatment, patients continued to use a stable dosage of their concomitant antidepressants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| REL-1017 | Experimental | Roll-over participants received 25 mg REL-1017 (one 25 mg REL-1017 tablet), orally, per day, either as a monotherapy or in addition to their ongoing antidepressant (ADT), rolling over from the monotherapy study REL-1017-303 or the adjunctive therapy studies REL-1017-301 and REL-1017-302, respectively. De Novo participants received a 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) on Day-1 of the 365-day treatment period. From Day-2 to Day-365, participants received 25 mg REL-1017 either as monotherapy or as adjunctive therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| REL-1017 | Drug | REL-1017 tablet |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs) | Subjects with at least one Treatment Emergent Adverse Events (TEAEs) | 52 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3 | Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 3. A negative change from baseline indicates shortening of the QTcF. | 3 Month |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the MADRS10 Total Score From Baseline to Month 3 | Therapeutic efficacy of REL-1017 in the Montgomery-Asberg Depression Rating Scale (MADRS10) A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 with scores above 34 indicating severe depression. A negative change from baseline indicates improvement. | 3 Month |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marco Pappagallo, MD | Relmada Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Relmada Site | Miami | Florida | 33015 | United States | ||
| Relmada Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39999772 | Derived | Fava M, Pani L, De Martin S, Cutler AJ, Gorodetzky CW, Vocci FJ, Sapienza FL, Kosten TR, Kroger C, Champasa P, Guidetti C, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M. Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder: Findings From a 12-Month Open-Label Study. J Clin Psychiatry. 2025 Feb 17;86(1):24m15438. doi: 10.4088/JCP.24m15438. |
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| ID | Title | Description |
|---|---|---|
| FG000 | REL-1017 | Roll-over participants received 25 mg REL-1017 (one 25 mg REL-1017 tablet), orally, per day, either as a monotherapy or in addition to their ongoing antidepressant (ADT), rolling over from the monotherapy study REL-1017-303 or the adjunctive therapy studies REL-1017-301 and REL-1017-302, respectively. De Novo participants received a 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) on Day-1 of the 365-day treatment period. From Day-2 to Day-365, participants received 25 mg REL-1017 either as monotherapy or as adjunctive therapy. REL-1017: REL-1017 tablet |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Safety Analysis Set: All participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | REL-1017 | Total participants in Open Label Study, including: Roll-over participants, rolling over from the monotherapy study REL-1017-303 or the adjunctive therapy studies REL-1017-301 and REL-1017-302, respectively. De Novo participants receiving REL1017 as either monotherapy or as adjunctive therapy. REL-1017: REL-1017 tablet |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety and Tolerability of REL-1017 as Incidence of Treatment Emergent Adverse Events (TEAEs) | Subjects with at least one Treatment Emergent Adverse Events (TEAEs) | Safety Analysis Set: All participants who received at least 1 dose of study drug. | Posted | Number | participants | 52 weeks |
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A Treatment Emergent Adverse Event (TEAE) is defined as an Adverse Event (AE) that starts or worsens at any time after initiation of study drug collected up to 1 month post treatment (Day 395) as collected in the Safety Analysis Set.
A TEAE is defined as an AE that starts or worsens at any time after initiation of study drug collected up to 1 month post treatment (Day 395) as collected in the Safety Analysis Set.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | REL-1017 | Total participants in Open Label Study REL-1017: REL-1017 tablet | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Coronary artery disease | Cardiac disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marco Pappagallo, MD | Relmada Therapeutics | 786-638-7384 | info@relmada.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 4, 2022 | Apr 17, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6 |
Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 6. A negative change from baseline indicates shortening of the QTcF. |
| 6 Month |
| Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12 | Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 12. A negative change from baseline indicates shortening of the QTcF. | 12 Month |
| Change in Diastolic Blood Pressure From Baseline to Month 3 | Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Diastolic Blood Pressure. | 3 Month |
| Change in Diastolic Blood Pressure From Baseline to Month 12 | Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Diastolic Blood Pressure. | 12 Month |
| Change in Systolic Blood Pressure From Baseline to Month 3 | Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Systolic Blood Pressure. | 3 Month |
| Change in Systolic Blood Pressure From Baseline to Month 12 | Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Systolic Blood Pressure. | 12 Month |
| Change in Heart Rate From Baseline to Month 3 | Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Heart Rate. | 3 Month |
| Change in Heart Rate From Baseline to Month 12 | Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Heart Rate. | 12 Month |
| Change in Weight From Baseline to Month 3 | Overall Safety of REL-1017 as measured by Weight From Baseline to Month 3. A negative change from baseline indicates a reduction in Weight. | 3 Month |
| Change in Weight From Baseline to Month 12 | Overall Safety of REL-1017 as measured by Weight From Baseline to Month 12. A negative change from baseline indicates a reduction in Weight. | 12 Month |
| Change in the MADRS10 Total Score From Baseline to Month 12 | Therapeutic efficacy of REL-1017 in the Montgomery-Asberg Depression Rating Scale (MADRS10) A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 with scores above 34 indicating severe depression. A negative change from baseline indicates improvement. | 12 Month |
| Miami |
| Florida |
| 33175 |
| United States |
| Relmada Site | Orlando | Florida | 32801 | United States |
| Relmada Site | Palm Bay | Florida | 32905 | United States |
| Relmada Site | Chicago | Illinois | 60634 | United States |
| Relmada Site | Chicago | Illinois | 60640 | United States |
| Relmada Site | Boston | Massachusetts | 02116 | United States |
| Relmada Site | Watertown | Massachusetts | 02472 | United States |
| Relmada Site | Staten Island | New York | 10312 | United States |
| Lost to Follow-up |
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| Protocol Violation |
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| Physician Decision |
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| Pregnancy |
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| Non-Compliance with Study Drug |
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| Non-Compliance with Study Schedule |
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| Study Completed by Sponsor |
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| Other |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Secondary | Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 3 | Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 3. A negative change from baseline indicates shortening of the QTcF. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 3. | Posted | Mean | Standard Deviation | ms | 3 Month |
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|
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| Secondary | Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 6 | Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 6. A negative change from baseline indicates shortening of the QTcF. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 6. | Posted | Mean | Standard Deviation | ms | 6 Month |
|
|
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| Secondary | Change in the QT Interval With Fridericia's Correction (QTcF) Interval From Baseline to Month 12 | Cardiac Safety of REL-1017 as measured by the Change in the QT interval with Fridericia's correction (QTcF) Interval From Baseline to Month 12. A negative change from baseline indicates shortening of the QTcF. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 12. | Posted | Mean | Standard Deviation | ms | 12 Month |
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| Secondary | Change in Diastolic Blood Pressure From Baseline to Month 3 | Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Diastolic Blood Pressure. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 3. | Posted | Mean | Standard Deviation | mmHg | 3 Month |
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| Secondary | Change in Diastolic Blood Pressure From Baseline to Month 12 | Cardiac Safety of REL-1017 as measured by the Diastolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Diastolic Blood Pressure. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 12. | Posted | Mean | Standard Deviation | mmHg | 12 Month |
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| Secondary | Change in Systolic Blood Pressure From Baseline to Month 3 | Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Systolic Blood Pressure. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 3. | Posted | Mean | Standard Deviation | mmHg | 3 Month |
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| Secondary | Change in Systolic Blood Pressure From Baseline to Month 12 | Cardiac Safety of REL-1017 as measured by the Systolic Blood Pressure (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Systolic Blood Pressure. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 12. | Posted | Mean | Standard Deviation | mmHg | 12 Month |
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| Secondary | Change in Heart Rate From Baseline to Month 3 | Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 3. A negative change from baseline indicates a reduction in Heart Rate. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 3. | Posted | Mean | Standard Deviation | beats/min | 3 Month |
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| Secondary | Change in Heart Rate From Baseline to Month 12 | Cardiac Safety of REL-1017 as measured by the Heart Rate (Supine/Semi-Supine) From Baseline to Month 12. A negative change from baseline indicates a reduction in Heart Rate. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 12. | Posted | Mean | Standard Deviation | beats/min | 12 Month |
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| Secondary | Change in Weight From Baseline to Month 3 | Overall Safety of REL-1017 as measured by Weight From Baseline to Month 3. A negative change from baseline indicates a reduction in Weight. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 3. | Posted | Mean | Standard Deviation | kg | 3 Month |
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| Secondary | Change in Weight From Baseline to Month 12 | Overall Safety of REL-1017 as measured by Weight From Baseline to Month 12. A negative change from baseline indicates a reduction in Weight. | Safety Analysis Set: All participants who received at least 1 dose of study drug and were assessed for the secondary safety endpoint at both Baseline and Month 12. | Posted | Mean | Standard Deviation | kg | 12 Month |
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| Other Pre-specified | Change in the MADRS10 Total Score From Baseline to Month 3 | Therapeutic efficacy of REL-1017 in the Montgomery-Asberg Depression Rating Scale (MADRS10) A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 with scores above 34 indicating severe depression. A negative change from baseline indicates improvement. | Full Analysis Set (FAS) at Month 3: All participants who received at least 1 dose of study drug and had at least one post-Baseline efficacy assessment, irrespective of any deviation from the protocol or premature discontinuation at Month 3. | Posted | Mean | Standard Deviation | units on a scale | 3 Month |
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| Other Pre-specified | Change in the MADRS10 Total Score From Baseline to Month 12 | Therapeutic efficacy of REL-1017 in the Montgomery-Asberg Depression Rating Scale (MADRS10) A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 with scores above 34 indicating severe depression. A negative change from baseline indicates improvement. | Full Analysis Set (FAS) at Month 12: All participants who received at least 1 dose of study drug and had at least one post-Baseline efficacy assessment, irrespective of any deviation from the protocol or premature discontinuation at Month 12. | Posted | Mean | Standard Deviation | units on a scale | 12 Month |
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| 624 |
| 8 |
| 624 |
| 142 |
| 624 |
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| Tachycardia | Cardiac disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Alcohol abuse | Psychiatric disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Anxiety | Psychiatric disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Anaphylactic reaction | Immune system disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Bacteraemia | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Pyelonephritis | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Hyperreflexia | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Tremor | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Sepsis | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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| Headache | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
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| Upper respiratory tract infections | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment | Not related to study drug. |
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